Approximately 10,000 people in the United States die from severe burns every year. Life-threatening burns occur in significant numbers in every form of military engagement and at every level of service. A critical need exists to improve survival rates and the standard of care for such burned patients and to reduce costs of treatment.
Surgical excision of the burn wound and application of an autograft taken from the patient's unburned skin is the routine method to treat patients with extensive burn injuries in the United States. Alternatively, when only small areas of unburned autograft skin are available for wound coverage, human cadaveric skin allograft, either cryopreserved or fresh, is currently the standard biologic dressing for coverage of extensive excised burn wounds (Atnip and Burke, 1983, Curr Prob. Surg. 20:623-86; Pruitt and Levine, 1984, Arch. Surg. 119:312-22; Hansbrough, 1987, In: Boswick J, ed. The Art and science of Burn Care. Rockville, Md.: Aspen Publ. Inc., 57-63). The performance of cryopreserved allograft skin on wounds is inferior to that of fresh skin, probably due to the loss of viability of keratinocytes and fibroblasts following cryopreservation, freezing and subsequent thawing. In addition, disruption of some of the physical composition of skin, such as basement membrane structures, by cryopreservation procedures may also contribute to decreased cell viability.
While fresh cadaveric skin allograft is the superior covering for excised wounds when autograft skin is not available, fresh skin is in limited supply. Another problem with cadaveric allograft skin is that it elicits host immunological rejection within several weeks of placement, although survival may be prolonged in the severely burned patient who become markedly immune suppressed secondary to the injury (Ninnemann et al., 1978, Transplantation 25:69-72). In patients with massive burn injury, this poses a significant problem because several months may be required for limited donor sites to heal in order to permit reharvesting of the patient's own skin for autografts to accomplish complete wound closure. Rapid rejection of allograft skin would necessitate its repeat application; unfortunately, rejection is frequently accompanied by bacterial colonization and infection of the wounds which can limit subsequent engraftment of both allogeneic and autologous skin. Additionally, subsequent allograft applications frequently undergo accelerated rejection, as a result of previous sensitization of the recipient's immune system. Care of patients with extensive burns thus becomes a race against time to achieve adequate graft coverage before life-threatening infections and other complications occur. Consequently, in this haste, the autograft skin is usually meshed and stretched widely so that it can cover large wound areas. Such meshing and stretching always result in extensive and unsightly mesh patterns of the healed skin, with accompanying scarring and contractions that remain permanently. This may even require reconstructive surgery over many years.
Other problems also accompany the use of cadaveric allograft skin. The costs and complexities of managing clinical skin banks are considerable (May and DeClement, 1981, J Burn Care Rehab 2:7-23; May and DeClement, 1981, J. Burn Care Rehab. 2:64-76; May and DeClement, 1981, J Burn Care Rehab 2:128-41), resulting in high costs of allograft skin (usually from $.50 to $1.00 per cm2), a price which frequently does not cover the actual costs of skin procurement, preservation, storage and distribution and quality-control. Allograft skin, particularly fresh, is in short supply due to limited numbers of referred and qualifying donors.
In addition, the potential for infectious disease transmission accompanying the use of cadaveric allograft skin is always present. Infection may be in the form of bacteria (Monafo and Bradley, 1976, J. Am. Med. Assoc. 235:1248-9; Blood et al., 1979, Proc. 11th Am. Burn Assoc. Mtg. 79-80; White et al., 1991, Am. Surg. 57:402-7; May and DeClement, 1981, J. Burn Care Rehab. 2:64-76), fungi or viruses (Simonds et al., 1992, N. Engl. J. Med. 326:726-32; Clarke, 1987, Lancet 1:983). In particular, human immunodeficiency virus (HIV) transmission is possible even with properly-screened skin, since the donor may have been infected but is tested during a period when the viral infection is not detectable in the blood utilizing current assays (Simonds et al., 1992, N. Engl. J. Med. 326:726-32). In view of the foregoing problems with cadaveric skin, there is a need for a superior alternative temporary skin replacement for the treatment of extensively burned patients. Ideally, such a substitute for cadaveric skin should adhere to the wound rapidly and reproducibly, persist long-term without rejection, and be readily available in large amounts.